CNS infections (Gianani)

Question 1

Infectious diseases by class of organism

Answer 1

Prion
Viral
Bacterial
Fungal
Protozoan
Helminthic

Post-infectious (autoimmune)

Question 2

Description of infection by site

Answer 2

Epidural or subdural abscess

Subdural empyema and brain abscess

Meningo -encephalitis

Question 3

Bacteria, fungi, viruses or parasites may invade the nervous system and locate in either the dura, leptomeninges, brain or spinal cord.

Answer 3

• Extradural or subdural infections from sinusitis, otitis, open skull fractures, endocarditis or lung abscesses are usually caused by pyogenic bacteria.

Question 4

Infection in the subdural space is called

Answer 4

meningitis. (The same word is used for neoplastic spread in the subarachnoid space as in “lymphomatous meningitis” or “carcinomatous meningitis”).

Question 5

intracerebral abscess vs encephalitis vs meningoencephalitis

Answer 5

In the brain, a localized infection may occur as an intracerebral abscess. When not so localized, an infection of the brain is known as an encephalitis or cerebritis, one of the spinal cord as a myelitis, and one affecting both as an encephalomyelitis.

By convention, the term encephalitis refers to viral infections of the brain.

Many infections involve both the subarachnoid space and the brain parenchyma. They are called meningoencephalitis

Question 6

Subdural Abscess (Subdural Empyema)

Answer 6

Infection may spread to the subdural space from air sinuses or from the middle ear.
The subdural space is traversed by bridging arteries and veins but has no vascular network of its own. Therefore, ** antibiotics have no access to this space.
Treatment of the subdural abscess consists of evacuation plus intravenous antibiotics.
Epidural and subdural abscesses are collections of pus.
If they are large enough, they compress the brain and spinal cord, resulting in loss of function and increased intracranial pressure.

Question 7

Meningitis Risk factors in adults and children include:

Answer 7

Local infection
Recent brain surgery
Recent head injury 
Spinal abnormalities
CSF shunt placement
Urinary tract infections/UT abnormalities
Weakened immune system

Question 8

Bacterial Meningitis

Answer 8

infection of the arachnoid membrane, subarachnoid space, and cerebrospinal fluid by bacteria. The subarachnoid space is bounded externally by the arachnoid membrane and internally by the pia, and dips into the brain along blood vessels in the perivascular (Virchow-Robin) spaces. It extends from the optic chiasm to the cauda equina and surrounds the brain and spinal cord completely.

The infection may –> meninges from an adjacent infected area such as sinusitis, otitis media, and mastoiditis or from the environment through a penetrating injury or congenital defect, such as a menigomyelocele. Most commonly, however, meningitis results from hematogenous dissemination of bacteria.

Question 9

The most common organisms of bacterial meningitis in children and adults

Answer 9

Streptococcus pneumoniae and Neisseria meningitidis.

Streptococcus pneumoniae is declining after the introduction of conjugated vaccines. Hemophilus influenzae, once very common in children, is now rare thanks to vaccination. In newborns, the most common organisms are beta hemolytic Streptococcus group B (Streptococcus agalactiae) and Escherichia coli. In babies, group B streptococcal infection is frequently acquired during passage through the birth canal but meningitis may also develop a few days or weeks after birth. Nosocomial sources of meningitis include craniotomy, internal and external ventricular shunts, penetrating cranial fractures, closed head injuries with CSF-leaking basilar skull fractures, external lumbar catheters, and rarely lumbar puncture.

Question 10

normal CSF findings

Answer 10

Pressure under 200 mm H2O
Protein 14-45 mg%
Glucose >50% serum
WBCs 0-10

Question 11

Purulent CSF findings

Answer 11

pressure&raquo_space;200
Protein 45-200
very low glucose, maybe 0
WBCs: 1000s

Question 12

Aseptic (viral) CSF findings

Answer 12

normal to slight increase in pressure
normal to slight increase protein
normal glucose
WBC: monos 10-100s

Question 13

Lumbar puncture

Answer 13

• direct access to the subarachnoid space of the lumbar cistern.
• obtain samples of CSF
• measure CSF pressure
• remove CSF in cases of suspected normal pressure hydrocephalus
• introduce drugs (such as antibiotics or cancer chemotherapy) or radiological contrast material into the CSF.

First, patient should be evaluated for evidence of elevated intracranial pressure: CT scan first to avoid risk of herniation.

Also, caution should be used in cases of impaired coagulation because of the risk of iatrogenic spinal epidural hematoma, which can compress the cauda equina.

Use Sterile technique under local anesthesia. A hollow spinal needle is introduced through the skin with a stylet occluding the lumen to prevent the introduction of skin cells into CSF during needle insertion.

Question 14

Lumbar puncture needle passes through

Answer 14

subcutaneous tissues, ligaments of the spinal column, dura, and arachnoid, to finally encounter CSF in the subarachnoid space of the lumbar cistern.

Note that the lumbar cistern is normally in direct communication with CSF in the ventricles and CSF flowing over the surface of the brain. The procedure may be done in the lying or seated position. A manometer tube is used to measure CSF pressure. Pressure measurements are more reliable in the lying position because in the seated position the entire column of CSF in the spinal canal adds to the pressure measured in the lumbar cistern. Normal CSF pressure in adults is less than 20 cm H2O.

Question 15

conus medullaris location

Answer 15

the bottom portion of the spinal cord, or conus medullaris, ends at about the L1 or L2 level of the vertebral bones, and the nerve roots continue downward into the lumbar cistern, forming the cauda equina, meaning “horse’s tail” (see Figure 5.22B). To avoid hitting the spinal cord, the spinal needle is generally inserted at the space between the L4 or L5 vertebral bones. As the tip of the needle enters the subarachnoid space, the nerve roots are usually harmlessly displaced. The posterior iliac crest serves as a landmark to determine the approximate level of the L4–L5 interspace.

Question 16

Acute bacterial meningitis clinical picture

Answer 16

acute onset (hours), fever, lethargy, headache, altered mental status, signs of meningeal irritation, such as neck stiffness. 

Of all infections of the central nervous system, acute purulent (bacterial) leptomeningitis is the most common. Purulent leptomeningitis (often simply called meningitis) still has an overall mortality of 10-15%, often as a result of diffuse cerebral edema and herniation. In survivors, long-term sequelae are not uncommon.

Question 17

acute bacterial meningitis clinical findings

Answer 17

The initial symptoms of meningitis are fever, severe headache, and stiff neck. The inflamed spinal structures are sensitive to stretch, and pain can be elicited by maneuvers that stretch the spine, such as bending the leg with an outstretched knee (Kernig sign) or bending the neck (Brudzinski sign). As the disease progresses, confusion, coma, and seizures develop. These complications are due to HIE, increased intracranial pressure, and a toxic metabolic encephalopathy. HIE is due to shock. The toxic metabolic encephalopathy is probably caused by unknown diffusible substances (perhaps cytokines) that have a neurotoxic action. In infants, meningitis may present with nonspecific signs such as a depressed state, apneic spells, changes in heart rate, and atypical seizures.

Question 18

Pathogenesis of bacterial meningitis (and inflammatory reaction)

Answer 18

• colonize the nasopharynx. –> blood stream –> subarachnoid space
• porous structure of choroid plexus capillaries facilitates their spillage into the CSF.
• The CSF provides enough nutrients for their multiplication and has few phagocytic cells, and low levels of antibodies and complement.

bacteria multiply uninhibited

Bacterial toxins –> neuronal apoptosis, cell wall lipopolysaccharide, released from bacteria–> damage to blood brain barrier (BBB).

Increased vascular permeability from BBB damage–> cerebral edema, increased intracranial pressure, decreased cerebral perfusion, hypoxia, and neuronal necrosis.

Cells of innate immune system of the brain, in the BBB, choroid plexus, and ependyma, detect bacteria and secrete cytokines, chemokines, and complement, which attract circulating neutrophils into the CSF.

Neutrophils have powerful lysosomal enzymes + free radicals, which they use to kill bacteria, but have a short life span. As they lyse, these compounds are spilled and can destroy everything in their way. If neutrophils accumulate, they can damage brain tissue, nerves, and blood vessels.

Vasculitis and clotting –> cerebral infarcts.

So, brain damage in bacterial meningitis is caused in part by the direct action of bacteria and in part by the antibacterial inflammatory response. The brain has elaborate mechanisms for controlling inflammation but, in some cases, unbalanced defense reactions can cause severe injury.

Question 19

Diagnosis and Pathology

of meningitis

Answer 19

cornerstone of dx : CSF examination.

• hundreds, even thousands of neutrophils, teeming with organisms.
• protein is elevated and glucose is low (because it is consumed by inflammatory cells). The CSF:blood glucose ratio is lower than 50%.

Neutrophils in the subarachnoid space infiltrate and damage cranial nerves resulting in cranial nerve deficits, and invade leptomeningeal vessels causing phlebitis and arteritis with thrombosis and ischemic infarction. Sinovenous thrombosis may also occur. The thick fibrinopurulent exudate in the subarachnoid space organizes into fibrous tissue that blocks the exits of the fourth ventricle and impairs CSF circulation around the cerebral convexities. This causes hydrocephalus. These complications take time to develop and may appear after the inflammation has subsided. They may be prevented by prompt treatment. The effects of HIE and cerebral infarction are especially devastating in newborn babies in whom the brain can literally melt away.

Question 20

Virchow - Robbin space

Answer 20

The CSF flows/bathes the brain surface and fills the “Virchow-Robbin space”. This space, which surrounds the vessels, ends at the level of the capillaries. Thus, whatever is in the CSF is brought deep into the brain parenchyma (such as inflammatory cells). Under normal circumstances, the BB barrier is intact throughout this system.

Question 21

blood brain barrier

Answer 21

• no fenestrations or pinocytotic (transportation) vesicles
• tight and adherens junctions
• different receptors and ion channels on their surface facing the lumen than on the surfaces facing the brain, an arrangement that facilitates transcellular transport.

—> blood-brain barrier (BBB).
endothelial cells surrounded by pericytes, and these vascular cells are enclosed within a basement membrane made up of collagens, laminins, and proteoglycans.

Astrocytic processes cover the capillaries, and perivascular macrophages are interposed between them and the capillary basement membrane.

The BBB separates plasma from the interstitial space of the CNS and is key to maintaining homeostasis in the CNS.

• controls the traffic of molecules, including ions and water in and out of the brain
• plays an important role in supplying the brain with nutrients and getting rid of waste and toxic products.

Lipophilic compounds cross the BBB easier than hydrophilic ones do, and small lipophilic molecules such as O2 and CO2 diffuse freely.

Question 22

The glia limitans

Answer 22

a thick tight mesh of astrocytic processes, joined by dense junctions and covered by basement membrane, resists penetration by bacteria and neutrophils. Undamaged, it provides an effective barrier that prevents the infection from spreading into brain tissue. Thus, brain abscess as a complication of meningitis is rare.

Question 23

BBB dysfunction.

Answer 23

A wide variety of disorders including stroke, trauma, CNS infections, demyelinative diseases, metabolic disorders, degenerative diseases, and malignant brain tumors are associated with BBB dysfunction.

end result of BBB dysfunction: increased vascular permeability –> vasogenic edema. E.g., blood vessels in GBM and other malignant brain tumors do not have tight junctions, explaining the fluid leakage and cerebral edema that accompanies these tumors.

Cytokines generated during infectious and inflammatory processes enhance transmigration of circulating leukocytes and may even loosen tight junctions, thus facilitating the migration of inflammatory cells into the brain. HIE disrupts the BBB. More subtle BBB dysfunction may result in impaired glucose transport and accumulation of Aβ.

Question 24

Common causes of bacterial meningitis related to age

Answer 24

Birth to two months: E. coli, Group B Streptococcus, Listeria

Two months to five years: Streptococcus pneumoniae, meningococcus. H. flu was a very common cause prior to development of a vaccine.

older child/adult: Streptococcus pneumoniae, Neisseria meningitidis (Meningococcus). Note: only form of bacterial meningitis that may occur in epidemics.***

Elderly: Streptococcus pneumoniae (Pneumococcus), E. coli, Group B Streptococcus, Listeria

Question 25

Cerebral Abscess - signs, spread

Answer 25

Headaches, fever, seizures, focal signs

Mortality 10 - 30% (even with appropriate therapy)

~50% of survivors with complications

Direct extension
- Trauma, surgery

Hematogenous
- Endocarditis, other infections

Question 26

Cerebral Abscess - defn and etiology

Answer 26

A Brain abscess is a collection of neutrophils and pus usually from bacterial or fungal infection.

A brain abscess rarely results from meningitis.

Usually it results from hematogenous dissemination of an infection.
Primary site of infection often not found.
Primary site often is lung.

Question 27

Why abscess is not a common complication of meningitis:

A. Because different bacteria are involved in the two processes.
B. Because the immune system prevent the spread of the infection to the brain.
C. Because the Glia Limitans protects the brain from the spread of the infection.
D. Because the Dura protects the brain from the spread of the infection.
E. Because the blood – brain membrane protects the glia from the spread of the infaction.

Answer 27

. Because the Glia Limitans protects the brain from the spread of the infection.

The brain is protected from bacterial invasion from the environment by the skull, the dura, the arachnoid membrane, the pia, and the glia limitans, which is a dense mesh of astrocytic processes on the surface of the brain. Consequently, most bacterial infections spread to the brain by the bloodstream. Bacteria can penetrate into the brain from the environment if there is a break in the continuity of these protective layers. Such a discontinuity may be due to congenital defects (encephalocele, meningomyelocele) or may be caused by trauma or a shunt. Bacteria can also spread to the brain from infected adjacent air sinuses, the middle ear and the mastoids. They can reach the brain either directly through the bone, especially in areas where the bone plate is thin, or through veins (diploic veins, dural venous sinuses, intracerebral veins). The various protective layers may also help contain infections within certain spaces or planes.
In the case of meningistis the glia limitans is the only barrier to the spread of the infection.

Question 28

What a brain looks like with Acute pneumococcal meningitis

Answer 28

• thick exudate, distributed here mainly at the vertex, coating the surface of the brain and obscuring the sulci. = many acute inflammatory cells (neutrophils) in the subarachnoid space.

neutrophils would also appear in the CSF removed by lumbar puncture.

• CSF glucose is typically decreased with acute bacterial meningitis.

Question 29

microscopic look of Acute pneumococcal meningitis

Answer 29

• a thick layer of polymorphonuclear leukocytes in the subarachnoid space in acute bacterial meningitis.
• inflammatory cells in the subarachnoid space can lead to cerebral edema.

Question 30

Acute aseptic (viral) meningitis: clinical picture, causative organism

Answer 30

Clinical picture – Similar to bacterial meningitis with fever, lethargy, headache, altered mental status and signs of meningeal irritation.

Enteroviruses are the most common organism

Low mortality

Question 31

Diff’l dx of lymphocyte-predominant “aseptic” meningitis

Answer 31

viral infections (incl. HIV)
partially treated bacterial meningitis
tuberculous meningitis
cryptococcal meningitis and othe rfungal infections
parameningeal infection (e.g. epidural abscess)
postinfectious encephalomyelitis
postvaccination encephalomyelitis
myelitis
lyme disease
neurosyphilis
parasitic infections (eosinophils may also be present)
carcinomatous (or other neoplastic) meningitis
central nervous system vasculitis
sarcoidosis
Venous sinus thrombosis
Subarachnoid hemorrhage several days previously
drug reaction
chemical irritation (e.g. from contrast material infected in CSF)

Question 32

Viral encephalitis- agents

Answer 32

Common agents:
Arboviruses
CMV(intranuclear inclusions)
Herpes(intranuclear inclusions)
HIV

Rare in the real world, but common on tests:
Rabies
PML (Progressive Multifocal Leukoencephalopathy)
- intranuclear inclusions
SSPE (Subacute Sclerosing Panencephalitis)

Question 33

A wide variety of different viruses can infect the CNS.

Answer 33

Most viruses are capable of causing either meningitis or encephalitis,

subset, including mumps, measles, varicella-zoster virus (VZV), rubella, and influenza –> postinfectious encephalitis.

A common cause of sporadic encephalitis is herpes simplex virus type 1.

Other diagnostic considerations will depend on geographic location (eg, St. Louis encephalitis in North America and Japanese encephalitis in Asia) and epidemiologic clues such as exposure history (eg, bat exposure or dog bite and rabies), regional outbreaks (eg, enterovirus type 71 in Denver, Colorado), and clinical clues such as profound weakness and rash with West Nile.

For many viral diseases the histologic changes are subtle and the diagnosis is made serologically (by a rise in specific antibody titers).

Question 34

Herpes Encephalitis

Answer 34

Headache, fever, neck stiffness, drowsiness, coma or focal neurologic signs (e.g. dysphasia, hemiparesis, seizures)

Without treatment, the disease progresses rapidly over the course of a few days and is usually fatal (~20%).

Fatal without immediate Rx in days
25-50% die regardless of Rx

Some patients do survive, with behavioral abnormalities, memory disturbances, and other neurologic deficits of varying severity.

Question 35

what the brain looks like in Herpes simplex encephalitis

Answer 35

• diffuse softening and edema
• hemorrhagic necrosis of the inferior frontal and temporal lobes.
• Microscopic: mononuclear cells, activated microglia, microglial nodules, and intranuclear inclusions.

–> extensive necrosis, macrophage reaction and neovascularization

end-stage: brain atrophy and gliosis.

Question 36

Adult and pediatric (post-neonatal) HSV encephalitis is caused most commonly by

Answer 36

HSV type I.
year-round
Most primary HSV infection- in their teens or twenties.
transmitted by the saliva. –> stomatitis. –> latent in the trigeminal ganglion. –> reactivated virus can spread either to the skin, along the branches of the trigeminal nerve, causing sores on the lips (herpes labialis), or to the brain, infecting the meninges of the anterior and middle cranial fossae.

From the meninges, the virus extends to the adjacent brain where it affects the temporal and inferior frontal lobes first and more severely, and then spreads to the rest of the brain. Adult HSV encephalitis is limited to the brain.

symptoms: fever, confusion, coma, and seizures. In addition, because of the involvement of the frontal and temporal lobes, patients often display bizarre behavior, personality changes, anosmia, and gustatory hallucinations. Survivors may have Korsakoff’s amnesia, because of bilateral damage of the hippocampus, dementia, and seizures.

Question 37

Neonatal HSV encephalitis.

Answer 37

Most: HSV-2 (herpes genitalis) and thirty percent by HSV-1. HSV-1 is most commonly aquired during vaginal delivery by contact with secretions in the infected birth canal.

Most infected mothers are symptomatic. Cesarean delivery before rupture of membranes prevents these infections.

• can be transmitted across the placenta.
• A few babies also acquire the infection after birth, in the newborn nursery or at home.

Untreated, neonatal HSV infection disseminates and involves the brain in most cases. The generalized infection affects the skin, eyes, liver, adrenal glands and other organs and presents clinically as neonatal sepsis.

Encephalitis (lethargy progressing to coma, seizures, mononuclear CSF pleocytosis with elevated protein) develops one or two weeks after birth, sometimes later.

• diffuse necrotizing pathology, without predilection for the frontal and temporal lobes. In time, the lesions evolve into cystic encephalomalacia with microcephaly.
• dx made by PCR of CSF.
• Treatment with Acyclovir significantly reduces mortality.

Question 38

Fetal CMV encephalitis looks like

Answer 38

Microcephaly, abnormal gyral pattern, hydrocephalus, and perivantricular calcificatiions.

Periventricular calcifications, ventriculomegaly and an abnormal gyral pattern.

Question 39

pregnancy and CMV

Answer 39

may transmit the virus to the fetus, causing a generalized fetal CMV infection. This infection may develop at any stage during pregnancy and may continue after delivery. Infants with congenital CMV infection have variable involvement of the brain and other organs.

Prenatal CMV infection often causes * necrosis of brain tissue, especially of the walls of the lateral ventricles. Necrotic areas calcify and can be detected by imaging. Infection before mid-gestation may derange the process of neuronal migration, causing microcephaly and cortical dysplasia. In some cases, fetal CMV infection destroys large parts of the brain, causing porencephaly, or schizencephaly. These lesions are thought to be caused by ischemia induced by the infection.

Question 40

Rabies

Answer 40

Rhabdovirus
Endemic in animals (foxes, raccoons, skunks, bats, dogs)
Animal bites, aerosols
Variable incubation period (10 days to a year)
Muscular replication
Centripetal axonal transport to CNS
Headaches, fever and malaise, swallowing difficulty
Furious form and “dumb” forms
Progresses to stupor, coma and death

Question 41

Rabies encephalitis

Answer 41

Rabies is still prevalent in many parts of the world. microscopic view demonstrates a Negri body which can be found in the cytoplasm of affected cells.

The most common site to find Negri bodies is within the Purkinje cells of the cerebellum or, as in this case, the pyramidal cells of the hippocampus. This virus travels intra-axonally from the site of the animal bite to the CNS and then spreads widely to cause the symptoms.

Question 42

Rabies microscopic buzzword

Answer 42

Negri bodies = viral inclusions

Question 43

Progressive Multifocal Leukoencephalopathy (PML)

Answer 43

• Caused by a polyomavirus (one of two ubiquitous viruses, JC and BK)
  Infection in humans is generally asymptomatic.
  Latent in kidneys and B-cells in tonsils of most adults and in the brains of some.
  Reactivation within CNS or in peripheral tissues, with impaired immunity leading to widespread damage of the white matter.**

** Infects/destroys oligodendrocytes

Question 44

Progressive Multifocal Leukoencephalopathy (PML) symptoms

Answer 44

Focal neurologic deficits (dysarthria, limb weakness, visual disturbances, ataxia, personality changes, and occasionally seizures)
Usually progresses relentlessly over a few months, with increasing cognitive impairment
Almost invariably fatal
Treatment of underlying immunosuppression (e.g. of AIDS, with highly active anti-retroviral therapy) can lead to remission

Question 45

PML blathering

Answer 45

opportunistic infection seen in immunocompromised patients (for example AIDS patients or transplant patients). Many of the reactive astrocytes are large with bizarre nuclei. This patient developed progressive multifocal leukoencephalopathy (PML) after a heart transplant.

Ultrastructurally, the nuclei are completely filled with virions in progressive multifocal leukoencephalopathy (PML). Each small dot seen here in the nucleus represents a virion. This gives the nucleus a stippled, or finely granular, appearance by electron microscopy.

Progressive multifocal leukoencephalopathy (PML) is a disease of the white matter of the brain, caused by a virus infection that targets cells that make myelin–the material that insulates nerve cells (neurons). Polyomavirus JC (often called JC virus) is carried by a majority of people and is harmless except among those with lowered immune defenses. The disease is rare and occurs in patients undergoing chronic corticosteroid or immunosuppressive therapy for organ transplant, or individuals with cancer (such as Hodgkin’s disease or lymphoma). Individuals with autoimmune conditions such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosis – some of whom are treated with biological therapies that allow JC virus reactivation – are at risk for PML as well. PML is most common among individuals with HIV-1 infection / acquired immune deficiency syndrome (AIDS). Studies estimate that prior to effective antiretroviral therapy, as many as 5 percent of persons infected with HIV-1 eventually develop PML that is an AIDS-defining illness. However, current HIV therapy using antiretroviral drugs (ART), which effectively restores immune system function, allows as many as half of all HIV-PML patients to survive, although they may sometimes have an inflammatory reaction in the regions of the brain affected by PML. The symptoms of PML are diverse, since they are related to the location and amount of damage in the brain, and may evolve over the course of several weeks to months The most prominent symptoms are clumsiness; progressive weakness; and visual, speech, and sometimes personality changes. The progression of deficits leads to life-threatening disability and (frequently) death. A diagnosis of PML can be made following brain biopsy or by combining observations of a progressive course of the disease, consistent white matter lesions visible on a magnetic resonance imaging (MRI) scan, and the detection of the JC virus in spinal fluid.

Question 46

Progressive Multifocal Leukoencephalopathy (PML)…microscopic findings

Answer 46

intranuclear viral particles

Affects white matter…goes after cells that make myelin

Question 47

Subacute Sclerosing Panencephalitis (SSPE)

Answer 47

• rare condition in kids/ adolescents- years after acute measles (that usually happened before 2 years of age)
• problems in school, behavioral changes–> seizures, motor problems–> coma, death.
• CSF: increased IgG
• diffuse chronic encephalitis within both the grey and white matter
• gliosis
• • intranuclear inclusions. Sometimes with clear halo and others appeare to fill the entire nucleus.
• Margination of the chromatin
• on EM: elongated nucleocapsids of measles, e.g.

Question 48

CNS Involvement in AIDS

Answer 48

Direct: HIV encephalitis.
Indirect:
Infectious: Toxoplasmosis, Cryptococcus, PML.
Neoplastic: Lymphoma.

Question 49

Causes of altered mental status in AIDS and the CD count

Answer 49

Toxoplasmosis- under 100
Cryptococcus- under 50
primary lymphoma- under 100/ EBV transformation
PML- under 200
HIV dementia- under 200

Question 50

Other organisms causing meningitis or meningoencephalitis

Answer 50

Fungal organisms
- Cryptococcal meningitis

Mycobacteria

• M. tuberculosis or M. avium-intracellulare
• Common in patients with miliary TB
• Tends to involve the base of the brain

Question 51

Cryptococcosis

Answer 51

Hematogenous dissemination from lung
Usually in immunosuppression
Common life-threatening infection in AIDS
Meningitis with or without parenchymal cysts
Abscess (cryptococcomas)
Variable presentation and clinical course
India ink CSF

Question 52

how we stain cryptococcosis?

Answer 52

India Ink!!

Question 53

Tuberculosis

Answer 53

Approximately 300 to 400 cases of TB meningitis in the United States each year
Mycobacterium tuberculosis, M. bovis, BCG
* Meningeal signs and cranial nerve palsies
* Basal meningitis
* Granular meningeal surface
Tuberculomas…granulomas (0.5 to 10% of systemic TB cases)
Spinal epidural Tuberculosis (paraplegia of Pott)
Vasculitis.

Question 54

Cerebral abscess types

Answer 54

Bacterial

• Patients with infective endocarditis
• Wound infection (post-operative)

Fungal

Protozoal

• Toxoplasmosis
• Amoebic abscess

Question 55

Toxoplasma Gondii

Answer 55

protozoan parasite.
- ingestion of oocysts that are shed in cat feces. If a woman becomes infected by T. gondii during pregnancy, transplacental infection of the fetus with possible severe neurologic consequences may occur.

Infections in adults with an intact immune system is usually asymptomatic and as many as 50% of adults in the US have antibodies to toxoplama. In immunocompromized patient (usually AIDS patients or transplant patients), cerebral toxoplasmosis is a common cause of intracerebral mass lesions, as shown here. It is thought to represent reactivation of a latent infection.

Question 56

The micrograph of toxoplasmosis

Answer 56

Each cyst is filled with many Toxoplasma gondii organisms, called “bradyzoites” while within the cysts and “tachyzoites” when outside the cyst.

Question 57

Aspergillosis

Answer 57

This is one of the more common mycotic infections of the nervous system
Spores, pulmonary entry
Hematogenous dissemination
Direct invasion
Immunosuppression (leukemia)
hemorrhagic Infarcts and abscesses
Very high mortality rate even with appropriate therapy

Question 58

Amoebic infections

Answer 58

Amoebic infection occurs by two routes. Rarely fresh water organisms enter through the nose, invade the brain and produce an acute, rapidly growing abcess leading to death in a few days if not treated. More commonly, enteric amebiasis spreads through the blood usually to the liver and sometimes eventually to the brain. This produces a much more slowly progressive disease.

Question 59

Neurocysticercosis

Answer 59

Globally- commonest parasitic infection of the CNS and a leading cause of epilepsy worldwide
Cysticercus cellusosae, Taenia solium larvae

Pork meat => patients become definite host. Latin America (Africa, Asia, Europe)

Cysticercosis as intermediate host
Muscle, other organs
Variable manifestation, some asymptomatic
There is an inflammatory reaction following the parasite’s death
Eventual calcification

The clinical features are very varied depending upon the number and location of the cysts.
Focal or generalized seizures, papilledema, headache, vomiting and ataxia, vertigo, focal motor and sensory deficits, dementia, acute hydrocephalus, and occasionally, sudden death.

diagnosed by history in appropriate populations, by typical radiologic appearance, and by antibody tests of the serum and cerebrospinal fluid. Sometimes eosinophilia, parasites in the stool, and soft tissue calcifications on X-rays may be present as well. In questionable cases, biopsy may be necessary. The condition is treated with albendazole.

Question 60

Key points – Prion

Answer 60

CJD is a subacute progressive dementia

Prions are proteinaceous infectious agents

• No nucleic acid
• Not inactivated by usual ways to sterilize instruments

Diseases caused by prions can be infectious, hereditary and sporadic

Question 61

The human prion diseases are:

Answer 61

Creutzfeldt-Jakob disease. Sporadic- sCJD, familial- fCJD, iatrogenic- iCJD, and variant- vCJD).

Kuru. A now-extinct disease of New Guinea natives, transmitted by eating the brains of dead persons who had the disease.

Gerstmann-Straüssler-Scheinker syndrome (GSS). An autosomal dominant slowly progressive ataxia and dementia, characterized by widespread PrPTSE amyloid plaques throughout the CNS.

Fatal familial insomnia (FFI). An autosomal dominant sleep disorder with pathological lesions in the thalamus.

Question 62

Difference between PrC and PrSC

Answer 62

PrSC is a misfolded protein and can “spread”

Disease occurs when PrC undergoes a conformational change from its normal α-helix-containing isoform to an abnormal β-pleated sheet isoform, usually termed PrSC

Question 63

autoimmune encephalitis comes from

Answer 63

anti-NMDA receptor